Placement of a Catheter into the Transverse Sinus in Monitoring Intracranial Lesions: A Technical Note.

High intracranial pressure (ICP) can be induced by stroke, brain trauma, and brain tumor, and lead to cerebral injury. Monitoring the blood flow of a damaged brain is important for detecting intracranial lesions. Blood sampling is a better way to monitor changes in brain oxygen and blood flow than computed tomography perfusion and magnetic resonance imaging. This article describes how to take blood samples from the transverse sinus in a high ICP rat model. Also, it compares the blood samples from the transverse sinus and femoral artery/vein through blood gas analysis and neuronal cell staining. The findings may be of significance to the monitoring of the oxygen and blood flow of intracranial lesions.

1H-NMR-based metabolomics study on coronary heart disease with blood-stasis syndrome and phlegm syndrome. / 基于1H-NMRçš„å† å¿ƒç— è¡€ç˜€è¯ã€ç—°æµŠè¯çš„ä»£è°¢ç»„å­¦ç ”ç©¶.

OBJECTIVES: Coronary heart disease (CHD) is a serious threat to human health because of its high morbidity. It is very urgent to study the pathogenesis of CHD and the effective drug target. The purpose of this paper is using the 1H-nuclear magnetic resonance spectroscopy (1H-NMR) metabolomics technology to establish the metabolic fingerprint and find the potential biomarker metabolites of CHD with blood-stasis syndrome and phlegm syndrome, and to reveal the metabolic mechanism of Xuefu Zhuyu Decoction for the treatment of CHD with blood stasis syndrome. METHODS: The plasma samples of 69 patients with CHD blood-stasis syndrome, 60 patients with CHD phlegm syndrome, and 40 healthy volunteers were collected in this study. Based on the 1H-NMR metabolomics technology, the metabolic fingerprint of CHD with blood-stasis syndrome and phlegm syndrome was established. Multivariate statistical analysis methods including principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to find the potential biomarker metabolites of CHD with blood-stasis syndrome and phlegm syndrome. Xuefu Zhuyu Decoction was used to randomly selected blood-stasis syndrome patient. The plasma samples of pre-treatment and post-treatment were collected. 1H-NMR and multivariate statistical analysis were used to analyze the changes of metabolites in patients with CHD blood-stasis syndrome before and after Xuefu Zhuyu Decoction treatment. RESULTS: A total of 15 potential biomarkers were identified in the plasma of patients with CHD blood-stasis syndrome, including 3-hydroxybutyrate (3-HB), lactate, alanine, glutamate, glutamine, pyruvate,phosphatidylcholine (PC), glycerylphosphorylcholine (GPC), glycine, glucose, phenylalanine, citrate,tyrosine, formate,very low density lipoprotein (VLDL). The levels of glucose, 3-HB, and VLDL increased, while the levels of other 12 metabolites decreased. A total of 16 potential biomarkers were identified in the plasma of patients with CHD phlegm syndrome, including valine, lactate, alanine, N-acetyl-ß-glucosaminidase (NAG), glutamate, glutamine, pyruvate, creatine, choline, glycine, glucose, phenylalanine, citrate, histidine, tyrosine, and formate. The levels of glucose and choline increased, while the levels of other 12 metabolites decreased. After treatment with Xuefu Zhuyu Decoction, the levels of choline, phospholipids/glycerolipids, creatine, lipids, and citrate increased, while the level of lactate decreased in patients with CHD blood-stasis syndrome. CONCLUSIONS: 1H-NMR combined with multivariate statistical method could effectively establish the diagnostic model for CHD blood-stasis syndrome and CHD phlegm syndrome, and find the metabolites related to the syndrome type. The metabolic mechanism of Xuefu Zhuyu Decoction on CHD blood-stasis syndrome may be associated with regulation of lipid metabolism and energy metabolism.

ß-Asarone suppresses TNF-α expression through DNA methylation and c-Jun-mediated transcription modulation in scratch-injured neuronal cells.

This study aimed to investigate the role and possible mechanism of ß-asarone in regulating neuronal apoptosis and axonal regeneration. A scratch injury was applied to cell cultures of mouse primary cortical neurons to mimic neuronal injury. The neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling staining and western blot analysis of apoptosis-related proteins. The axonal regeneration was assessed by immunofluorescent staining of ß-tubulin III and western blot analysis of axonal markers. In the results, ß-asarone inhibited neuronal apoptosis and promoted axonal regeneration by suppressing tumor necrosis factor-α (TNF-α) expression in scratch-injured mouse neuronal cells. Research investigating the molecular mechanisms by which ß-asarone inhibited TNF-α expression showed that, on the one hand, ß-asarone suppressed the JNK/c-Jun pathway and thus transcriptionally inhibited TNF-α expression; on the other hand, ß-asarone induced expression of UHRF1 that recruited DNMT1 to induce TNF-α promoter methylation and subsequently decreased the messenger RNA expression of TNF-α. In conclusion, ß-asarone suppresses TNF-α expression through DNA methylation and c-Jun-mediated transcription modulation in scratch-injured neuronal cells.

Fengbaisan suppresses endoplasmic reticulum stress by up-regulating SIRT1 expression to protect rats with chronic obstructive pulmonary diseases.

CONTEXT: Our previous study found that Fengbaisan improved chronic obstructive pulmonary diseases (COPD). OBJECTIVE: To elucidate the mechanism of Fengbaisan in COPD. MATERIALS AND METHODS: Rats in Model, FBS, FBS + DMSO and FBS + EX527 groups received cigarette smoke extract (CSE) inhalation and intratracheal instillation of lipopolysaccharide to establish COPD model. Normal group received room air and normal saline. The COPD rats were given Fengbaisan (1 mL/d) or combined with EX527 (5 mg/kg/2 d) by intraperitoneal injection. Human lung carcinoma (A549) cells were treated with 10% CSE, 10% serum-containing Fengbaisan or EX527. We observed lung percentage of forced expiratory volume in first 0.3 sec to forced vital capacity (FEV0.3/FVC), inspiratory resistance (RI) and lung dynamic compliance (Cdyn) of rats. The lung pathological changes, the number of inflammatory cells and neutrophils, inflammatory factor, apoptosis, gene and protein expression were examined. RESULTS: SIRT1 was downregulated in lung tissues of COPD rats and CSE-induced A549 cells. Fengbaisan enhanced FEV0.3/FVC (74.28%) and Cdyn (0.28 cm H2O/mL/s), and reduced RI (0.48 mL/cm H2O) of COPD rats. Moreover, Fengbaisan promoted SIRT1 expression, and repressed TIMP-1/MMP-9 expression. Fengbaisan enhanced apoptosis and the expression of GRP78, caspase-12 and caspase-3. The inflammatory factor levels, the number of inflammatory cells and neutrophils, and lung lesions were inhibited by Fengbaisan in COPD rats. The influence conferred by Fengbaisan was abolished by EX527. DISCUSSION AND CONCLUSIONS: Fengbaisan inhibits endoplasmic reticulum stress and inflammation reaction by up-regulating SIRT1 expression to improve COPD. Therefore, Fengbaisan may be an effective Chinese medicine for treating COPD.

Downregulated lncRNA CRNDE contributes to the enhancement of nerve repair after traumatic brain injury in rats.

Objective: Long non-coding RNAs (lncRNAs) have recently been demonstrated to be involved in craniocerebral disease, but their expression in traumatic brain injury (TBI) is still unearthed. Therefore, we aimed to elucidate the effect of lncRNA CRNDE on TBI. Methods: Firstly, CRNDE expression was determined in serum of TBI patients and healthy controls. The TBI rat model was established based on Feeney's freefall impact method. The modeled rats were injected with siRNA against CRNDE, and the rats' neurobehavioral function were measured. Besides, expression of inflammatory factors, size, shape and number of hippocampal neurons, neuron apoptosis, Beclin I, LC3-I, LC3-II, glial fibrillary acidic protein (GFAP), BrdU, nerve growth factor (NGF), nestin, and neuronal nuclei (NeuN) expression were detected through different methods. Results: In TBI, CRNDE was found to be upregulated. Downregulated CRNDE improved neurobehavioral function, repressed expression of neuroinflammatory factors, elevated number of Nissl bodies, as well as restricted neuronal apoptosis and autophagy in TBI rats. Besides, downregulated CRNDE also promoted expression of GFAP, BrdU, NGF, nestin, and NeuN, thus induced the differentiation of neurons and the directional growth and regeneration of nerve fibers. Conclusion: Altogether, we found that silencing of CRNDE might be able to promote the nerve repair after TBI in rats.

Changqin NO. 1 inhibits neuronal apoptosis via suppressing GAS5 expression in a traumatic brain injury mice model.

The present study was designed to investigate the mechanism of the traditional Chinese medicine Changqin NO. 1 on the amelioration of traumatic brain injury (TBI). Adult male C57BL/6J mice and newborn mice were used to generate a mouse TBI model and harvest primary neurons, respectively. The localizations of specific neural markers neuropilin-1 (Nrp-1), growth-associated protein-43 (GAP-43) and microtubule-associated protein Tau (Tau) were examined in brain tissues by immunohistochemistry. Terminal deoxynucleotidyl transferase dUTP nick end labeling apoptotic cell detection in tissue sections and the CCK-8 cell viability assay were performed to examine neuronal apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were also carried out in this study. The association between long non-coding RNA (lncRNA) growth-arrest specific 5 (GAS5), miR-335 and RAS p21 GTPase activating protein 1 (Rasa1) was disclosed using the dual-luciferase reporter assay. Changqin NO. 1 inhibited TBI-induced neuronal apoptosis in vivo and in vitro. GAS5 functioned as a competing endogenous RNA (ceRNA) by sponging miR-335 to upregulate Rasa1 expression in mouse neuronal cells. Further investigations demonstrated that GAS5 promoted neuronal apoptosis following TBI via the miR-335/Rasa1 axis. In vivo experiments indicated that Changqin NO. 1 exerted neuroprotection during TBI via the GAS5/miR-335/Rasa1 axis. Changqin NO. 1 promoted neuroprotective effects by inhibiting neuronal apoptosis via the GAS5/miR-335/Rasa1 axis in TBI.

Hollow porous ionic liquids composite polymers based solid phase extraction coupled online with high performance liquid chromatography for selective analysis of hydrophilic hydroxybenzoic acids from complex samples.

Polar and hydrophilic properties of hydroxybenzoic acids usually made them coelute with interferences in high performance liquid chromatography (HPLC) analysis. Then selective analysis of them was necessary. Herein, hollow porous ionic liquids composite polymers (PILs) based solid phase extraction (SPE) was firstly fabricated and coupled online with HPLC for selective analysis of hydroxybenzoic acids from complex matrices. Hollow porous PILs were firstly synthesized using Mobil Composition of Matter No. 48 (MCM-48) spheres as sacrificial support, 1-vinyl-3-methylimidazolium chloride (VMIM+Cl-) as monomer, and ethylene glycol dimethacrylate (EGDMA) as cross-linker. Various parameters affecting synthesis, adsorption and desorption behaviors were investigated and optimized. Steady-state adsorption studies showed the resulting hollow porous PILs exhibited high adsorption capacity, fast adsorption kinetics, and excellent specific adsorption. Subsequently, the application of online SPE system was studied by selective analysis of protocatechuic acid (PCA), 4-hydroxybenzoic acid (4-HBA), and vanillic acid (VA) from Pollen Typha angustifolia. The obtained limit of detection (LOD) varied from 0.002 to 0.01µg/mL, the linear range (0.05-5.0µg/mL) was wide with correlation coefficient (R) from 0.9982 to 0.9994, and the average recoveries at three spiking levels ranged from 82.7 to 102.4%, with column-to-column relative standard deviation (RSD) below 8.1%. The proposed online method showed good accuracy, precision, specificity and convenience, which opened up a universal and efficient route for selective analysis of hydroxybenzoic acids from complex samples.

High Intracranial Pressure Induced Injury in the Healthy Rat Brain.

OBJECTIVES: We recently showed that increased intracranial pressure to 50 mm Hg in the healthy rat brain results in microvascular shunt flow characterized by tissue hypoxia, edema, and increased blood-brain barrier permeability. We now determined whether increased intracranial pressure results in neuronal injury by Fluoro-Jade stain and whether changes in cerebral blood flow and cerebral metabolic rate for oxygen suggest nonnutritive microvascular shunt flow. DESIGN: Intracranial pressure was elevated by a reservoir of artificial cerebrospinal fluid connected to the cisterna magna. Arterial blood gases, cerebral arterial-venous oxygen content difference, and cerebral blood flow by MRI were measured. Fluoro-Jade stain neurons were counted in histologic sections of the right and left dorsal and lateral cortices and hippocampus. SETTING: University laboratory. SUBJECTS: Male Sprague Dawley rats. INTERVENTIONS: Arterial pressure support if needed by IV dopamine infusion and base deficit corrected by sodium bicarbonate. MEASUREMENTS AND MAIN RESULTS: Fluoro-Jade stain neurons increased 2.5- and 5.5-fold at intracranial pressures of 30 and 50 mm Hg and cerebral perfusion pressures of 57 ± 4 (mean ± SEM) and 47 ± 6 mm Hg, respectively (p < 0.001) (highest in the right and left cortices). Voxel frequency histograms of cerebral blood flow showed a pattern consistent with microvascular shunt flow by dispersion to higher cerebral blood flow at high intracranial pressure and decreased cerebral metabolic rate for oxygen. CONCLUSIONS: High intracranial pressure likely caused neuronal injury because of a transition from normal capillary flow to nonnutritive microvascular shunt flow resulting in tissue hypoxia and edema, and it is manifest by a reduction in the cerebral metabolic rate for oxygen.

Critical cerebral perfusion pressure at high intracranial pressure measured by induced cerebrovascular and intracranial pressure reactivity.

OBJECTIVES: The lower limit of cerebral blood flow autoregulation is the critical cerebral perfusion pressure at which cerebral blood flow begins to fall. It is important that cerebral perfusion pressure be maintained above this level to ensure adequate cerebral blood flow, especially in patients with high intracranial pressure. However, the critical cerebral perfusion pressure of 50 mm Hg, obtained by decreasing mean arterial pressure, differs from the value of 30 mm Hg, obtained by increasing intracranial pressure, which we previously showed was due to microvascular shunt flow maintenance of a falsely high cerebral blood flow. The present study shows that the critical cerebral perfusion pressure, measured by increasing intracranial pressure to decrease cerebral perfusion pressure, is inaccurate but accurately determined by dopamine-induced dynamic intracranial pressure reactivity and cerebrovascular reactivity. DESIGN: Cerebral perfusion pressure was decreased either by increasing intracranial pressure or decreasing mean arterial pressure and the critical cerebral perfusion pressure by both methods compared. Cortical Doppler flux, intracranial pressure, and mean arterial pressure were monitored throughout the study. At each cerebral perfusion pressure, we measured microvascular RBC flow velocity, blood-brain barrier integrity (transcapillary dye extravasation), and tissue oxygenation (reduced nicotinamide adenine dinucleotide) in the cerebral cortex of rats using in vivo two-photon laser scanning microscopy. SETTING: University laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: At each cerebral perfusion pressure, dopamine-induced arterial pressure transients (~10 mm Hg, ~45 s duration) were used to measure induced intracranial pressure reactivity (Δ intracranial pressure/Δ mean arterial pressure) and induced cerebrovascular reactivity (Δ cerebral blood flow/Δ mean arterial pressure). MEASUREMENTS AND MAIN RESULTS: At a normal cerebral perfusion pressure of 70 mm Hg, 10 mm Hg mean arterial pressure pulses had no effect on intracranial pressure or cerebral blood flow (induced intracranial pressure reactivity = -0.03 ± 0.07 and induced cerebrovascular reactivity = -0.02 ± 0.09), reflecting intact autoregulation. Decreasing cerebral perfusion pressure to 50 mm Hg by increasing intracranial pressure increased induced intracranial pressure reactivity and induced cerebrovascular reactivity to 0.24 ± 0.09 and 0.31 ± 0.13, respectively, reflecting impaired autoregulation (p < 0.05). By static cerebral blood flow, the first significant decrease in cerebral blood flow occurred at a cerebral perfusion pressure of 30 mm Hg (0.71 ± 0.08, p < 0.05). CONCLUSIONS: Critical cerebral perfusion pressure of 50 mm Hg was accurately determined by induced intracranial pressure reactivity and induced cerebrovascular reactivity, whereas the static method failed.

Preparative isolation and purification of seven main antioxidants from Eucommia ulmoides Oliv. (Du-zhong) leaves using HSCCC guided by DPPH-HPLC experiment.

Seven antioxidants were purified from Eucommia ulmoides Oliv. leaves using HSCCC guided by DPPH-HPLC experiment. HSCCC was successfully used to separate target antioxidants by three runs with different solvent systems after D101 column chromatography fractionation. Ethyl acetate-n-butanol-water (1:2:3, v/v/v) was selected as the optimum solvent system to purify geniposidic acid. Ethyl acetate-ethanol-water (4:1:5, v/v/v) was used to isolate caffeic acid, chlorogenic acid and ferulic acid. While three flavonoids, quercetin-3-O-sambubioside, rutin and isoquercitrin were purified by petroleum ether-ethyl acetate-methanol-water (1:5:1:5, v/v/v/v). The structures were identified by MS and NMR. Antioxidant activities were assessed, and compounds 2-7 showed strong antioxidant activities. This is the first report about separation of antioxidants from E. ulmoides leaves by HSCCC. The results indicated that the combinative methods using DPPH-HPLC and HSCCC could be widely applied for screening and isolation of antioxidants from complex extracts.

KCNQ1 gene polymorphisms are associated with the therapeutic efficacy of repaglinide in Chinese type 2 diabetic patients.

The present study evaluated the effects of KCNQ1 rs2237892 and rs2237895 polymorphisms on repaglinide efficacy in Chinese patients with type 2 diabetes mellitus (T2DM). In all, 367 T2DM patients and 214 controls were genotyped. Forty of the T2DM patients were randomly selected to undergo 8 weeks repaglinide treatment. The frequency of the rs2237892 allele was lower in the T2DM patients than in the control group (P < 0.05). The frequency of the rs2237895 C allele was higher in T2DM patients than in healthy control subjects (P < 0.05). Diabetic patients with the rs2237892 risk C allele had lower fasting insulin levels (P < 0.01) and homeostasis model assessment of insulin resistance (HOMA-IR; P < 0.01) values than carriers of the T allele. Diabetic patients with the rs2237895 risk C allele had higher fasting plasma glucose (P < 0.01), postprandial plasma glucose (PPG) levels (P < 0.01) and HOMA-IR values (P < 0.01) than those with the A allele. Following repaglinide treatment, those T2DM patients with the rs2237892 T allele and rs2237895 C allele were more likely to have a positive response to repaglinide in terms of PPG levels (P < 0.05) than T2DM patients with the rs2237892 CC and rs2237895 AA genotypes. In conclusion, KCNQ1 rs2237892 and rs2237895 polymorphisms were found to be associated with the therapeutic efficacy of repaglinide in Chinese T2DM patients.

NeuroD1 A45T and PAX4 R121W polymorphisms are associated with plasma glucose level of repaglinide monotherapy in Chinese patients with type 2 diabetes.

AIMS: We aimed to determine whether NeuroD1/BETA2 and PAX4 polymorphisms were associated with the therapeutic efficacy of repaglinide in Chinese type 2 diabetes mellitus (T2DM) patients. METHODS: Three hundred and sixty-eight T2DM patients and 132 healthy control subjects were genotyped by restriction fragment length polymorphism. Forty-three patients with various genotypes were randomly selected to undergo 8 weeks of repaglinide treatment (3 mg day(-1)). Fasting plasma glucose, postprandial plasma glucose, glycated haemoglobin, fasting and postprandial serum insulin (FINS, PINS), homeostasis model assessment for insulin resistance, serum triglyceride, total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol were determined before and after repaglinide treatment. RESULTS: The allelic frequency of NeuroD1/BETA2 T45 was higher in T2DM patients than in the control subjects [13.45 vs. 6.82%, P < 0.01, odds ratios = 2.342 (1.365, 4.019), P= 0.002]. Type 2 diabetes mellitus patients with the mutated allele of NeuroD1/BETA2 A45T polymorphism showed higher FINS (13.46 ± 12.57 vs. 10.04 ± 7.09 mU l(-1) , P < 0.05) (11.67, 14.83 vs. 8.38, 11.37) and PINS (52.11 ± 40.93 vs. 68.66 ± 43.87 mU l(-1), P < 0.05) (44.89, 58.35 vs. 55.35, 88.87) than individuals with the T allele. The PAX4 R121W R allele carriers had higher PINS (52.11 ± 40.93 vs. 68.66 ± 43.87 mU l(-1), P < 0.05) (44.89, 58.35 vs. 55.35, 88.87) than subjects with the W allele. After repaglinide treatment, patients with the T allele of NeuroD1/BETA2 A45T polymorphisms had attenuated efficacy on fasting plasma glucose (-2.79 ± 2.14 vs.-0.99 ± 1.80 mmol l(-1), P < 0.01) (-3.53, -1.84 vs.-1.99, -0.13) and postprandial plasma glucose (-6.71 ± 5.90 vs.-2.54 ± 3.39 mmol l(-1), P < 0.01) (-9.28, -4.62 vs.-4.34, -0.84). Patients with the RR genotype of PAX4 R121W showed better efficacy with respect to the level of postprandial plasma glucose than R/W genotypes (-6.53 ± 6.52 vs.-2.95 ± 1.17 mmol l(-1), P < 0.05) (-8.20, -4.89 vs.-3.92, -1.20). CONCLUSIONS: The NeuroD1/BETA2 and PAX4 polymorphisms were substantially associated with plasma glucose level after repaglinide monotherapy.

Association of plasma epinephrine level with insulin sensitivity in metabolically healthy but obese individuals.

In the present study, we explored the association of catecholamines with insulin sensitivity in "metabolically healthy but obese" (MHO) individuals, by examining the metabolic characteristics and plasma catecholamine levels in 100 obese, sedentary postmenopausal women. Subjects were classified as MHO (n=25) or at-risk (n=25) based on the upper and lower quartiles of insulin sensitivity as measured by the hyperinsulinemic-euglycemic clamp technique. The MHO group presented a significantly higher range of plasma epinephrine levels (73 ± 21 pg/mL) than the at-risk group (39 ± 20 pg/mL) (P<0.05), though both within the normal basal range of plasma epinephrine (56 ± 30 pg/mL). Multivariate regression analysis showed that high-sensitivity C-reactive protein, plasma epinephrine, triglycerides and lean body mass index were independent predictors of glucose disposal. The plasma epinephrine level was positively correlated with the glucose disposal rate, insulin sensitivity and the HDL-cholesterol level, and negatively correlated with the triglycerides level (P<0.05). In conclusion, this study for the first time demonstrates a positive association between plasma epinephrine level and insulin sensitivity in MHO individuals.

Effect of nicotinamide mononucleotide on insulin secretion and gene expressions of PDX-1 and FoxO1 in RIN-m5f cells.

OBJECTIVE: To investigate the effect of nicotinamide mononucleotide (NMN) on insulin secretion and gene expressions of pancreatic and duodenal homeobox 1(PDX-1) and forkhead box-containing protein O-1 (FoxO1), which were important transcription factors for insulin secretion. METHODS: Insulin secretion level in RIN-m5f cells was detected by rat insulin ELISA detection kit. The mRNA expression levels of PDX-1 and FoxO1 in RIN-m5f cells were analyzed by real-time PCR. The protein expression of PDX-1 was measured by Western blot. RESULTS: Insulin secretion levels in RIN-m5f cells treated with repaglinide (10 nmol/L) plus NMN (100 µmol/L) was significantly higher than those in the blank control, the DMSO control group, and the NMN (50 µmol/L) treated group (P<0.05). The mRNA expression levels of PDX-1 in RIN-m5f cells treated with NMN (10, 50 and 100 µmol/L) for 36 h were significantly higher than those in the control group (P<0.05, P<0.01, and P<0.001, respectively). There was marked differences in the mRNA expression levels of PDX-1 among different concentrations of NMN (P<0.001), but no significant differences in the mRNA expression level of FoxO1 (P>0.05). No significant difference was found in the protein expression levels of PDX-1 in RIN-m5f cells treated by NMN (50, 100, and 200 µmol/L) for 36 or 48 h compared with the control group (P>0.05). CONCLUSION: NMN can stimulate insulin secretion and upregulate the mRNA expression of PDX-1 in RIN-m5f cells.

Impact of retinol binding protein 4 polymorphism on rosiglitazone response in Chinese type 2 diabetic patients.

OBJECTIVE: To explore the association between rs3758539G-803A and rs10882283T-179G polymorphism of retinol binding protein 4 (RBP4) and rosiglitazone response in Chinese type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 472 Chinese T2DM patients and 198 healthy subjects were enrolled to identify G-803A and T-179G genotypes using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Forty-two T2DM patients with different G-803A or T-179G genotypes were selected to undergo a 12-week rosiglitazone treatment (4 mg/d). Serum fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting serum insulin (FINS), glycated hemoglobin (HbAlc), postprandial serum insulin (PINS), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-c), and high-density lipoprotein-cholesterol (HDL-c) were determined before and after the rosiglitazone treatment. RESULTS: T2DM patients with RBP4 G-803A GG genotype showed lower TG and LDL-c concentrations compared with that in the GA+AA genotype subjects. T2DM patients with RBP4 T-179G TT genotype showed lower waist-to-hip ratio (WHR), FPG and FINS values compared with that in the TG+GG genotype individuals. Patients with GG genotype of RBP4 G-803A had an enhanced rosiglitazone efficacy on FPG and FINS compared with that in the GA+AA genotype group. Patients with RBP4 T-179G TG+GG genotype showed an enhanced rosiglitazone efficacy on HbAlc level compared with that in the TT genotype group. CONCLUSION: RBP4 G-803A and T-179G polymorphism might be associated with the development of T2DM and affect the therapeutic efficacy of rosignitazone in Chinese T2DM patients.

Serine racemase rs391300 G/A polymorphism influences the therapeutic efficacy of metformin in Chinese patients with diabetes mellitus type 2.

1. The aim of this study was to investigate the association of the serine racemase (SRR) rs391300 G/A polymorphism with the risk of diabetes mellitus type 2 (T2DM) and to assess the impacts of the polymorphism on the therapeutic efficacy of metformin in Chinese patients. 2. A case-control study of 402 patients with T2DM and 171 healthy controls was conducted. The SRR rs391300 polymorphism was genotyped in all participants using the ABI 3700 automated sequencer. Forty-four recent-onset T2DM patients with different rs391300 genotypes were selected to receive 500 mg metformin orally daily for 12 consecutive weeks as monotherapy. Serum fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated haemoglobin (HbA1c), fasting serum insulin (FINS), postprandial serum insulin (PINS), triglycerol (TG), cholesterol (CHO), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), homeostasis model assessment for insulin resistance (HOMA-IR), and body mass index (BMI) were determined before and after metformin treatment. 3. The distribution frequencies of rs391300 were in agreement with Hardy-Weinberg equilibrium (P > 0.05). After treatment with metformin, the values of BMI, FPG, PPG, PINS, HbA1c, CHO, and TG decreased significantly (P < 0.01), whereas FINS increased (P < 0.001), in patients with T2DM. Patients with the GA or AA genotype of rs391300 showed better improvements in the levels of FPG, PPG, and CHO (P < 0.05) than individuals with the GG genotype. 4. The SRR rs391300 polymorphism was associated with the therapeutic efficacy of metformin in Chinese patients with T2DM.

The protective effect of magnesium lithospermate B against glucose-induced intracellular oxidative damage.

OBJECTIVES: To investigate the effects of magnesium lithospermate B (LAB) on intracellular reactive oxygen species (ROS) production induced by high dose of glucose or H(2)O(2), we explored the influences of LAB on the expression of heme oxygenase-1 (HO-1) and nuclear factor E2-related factor-2 (Nrf2) in HEK293T cells after treatment with high dose of glucose. MATERIALS AND METHODS: The total nuclear proteins in HEK293T cells were extracted with Cytoplasmic Protein Extraction Kit. The ROS level was determined by flow cytometry. The mRNA and protein expression of HO-1 and Nrf2 were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. RESULTS: LAB reduced the ROS production in HEK293T cells cultured under oxidative stress. High dose of glucose enhanced the expression of HO-1 mRNA and HO-1 protein in a time-dependent manner. LAB enhanced the expression of HO-1 mRNA and HO-1 protein in a dose-dependent manner treated with high dose of glucose. The amount of Nrf2 translocation was enhanced after cells were pretreated with 50µmol/L or 100µmol/L LAB. Silencing of Nrf2 gene eliminated the enhanced expression of HO-1 protein induced by high dose of glucose plus LAB. CONCLUSIONS: LAB plays an important role against glucose-induced intracellular oxidative damage. The enhanced expression of HO-1 mRNA and HO-1 protein caused by LAB is regulated via Nrf2 signal pathway.

NAMPT -3186C/T polymorphism affects repaglinide response in Chinese patients with Type 2 diabetes mellitus.

1. In the present study, we investigated the associations of nicotinamide phosphoribosyltransferase (NAMPT)-3186 C/T and -948G/T polymorphisms with the risk of Type 2 diabetes mellitus (T2DM) and their impact on the efficacy of repaglinide in Chinese Han T2DM patients. 2. In all, 170 patients with T2DM and 129 healthy controls were genotyped for NAMPT-948G>T and -3186C>T polymorphisms. Thirty-five patients with different NAMPT -3186 C/T genotypes and the same organic anion-transporting polypeptide 1B1 (OATP1B1521) T/C genotype were randomly selected to undergo 8 weeks preprandial repaglinide treatment (1 mg, three times daily). Serum fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), glycated haemoglobin (HbAlc), fasting serum insulin (FINS), post-prandial serum insulin (PINS), triglyceride (TG), total cholesterol (CHO), homeostasis model assessment of insulin resistance (HOMA-IR), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) were determined before and after repaglinide treatment. 3. After repaglinide treatment for 8 consecutive weeks, there were significantly decreases in PFG, PPG, HbAlc, CHO and LDL-C, and increases in FINS, HDL-C and the HDL-C : LDL-C ratio, in T2DM patients. The elevated PINS value in patients with CT genotypes was significantly lower than that in patients with the CC and TT genotypes (P < 0.05) and there were significant differences in CHO between patients with the CT genotype and the CC or TT genotype (P < 0.05). 4. The data suggest that the NAMPT -3186C>T polymorphism is significantly associated with plasma levels of PINS and CHO in Chinese T2DM patients with repaglinide monotherapy.

A systematic review of RCTs and quasi-RCTs on traditional Chinese patent medicines for treatment of chronic hepatitis B.

Traditional Chinese patent medicines (TCPMs) are widely used for treatment of chronic hepatitis B (CHB) in China. To estimate the overall effectiveness of TCPMs for CHB, we performed a systematic review of clinical reports designed as randomized controlled trials (RCTs). One hundred and thirty-eight available RCTs and quasi-RCTs on 62 TCPMs, involving 16,393 patients, were included. The methodological quality of these trials was generally "poor". Few trials (6.52%) reported the methods of randomization correctly. Another common problem was the lack of allocation concealment, proper blinding, and the reporting of lost cases and dropouts. Forty-two trials (30.43%) on 27 TCPMs reported some anti-viral effect of TCPMs. Others reported beneficial aspects, including improvements of liver function (79.71% of the studies), liver fibrosis (29.99%), and CHB symptoms (92.75%). Forty-one articles (29.71%) reported mild adverse events with TCPMs but these occurred infrequently. In summary, the outcome of the report on currently registered TCPMs may be biased due to poor methodology. The data from these trials, therefore, is too weak to use in forming a recommendation for treatment of CHB. Nevertheless, five drugs (Dan Shen agents, Da Huang Zhe Chong pill/capsule, Shuang Hu Qing Gan granule, Fu Zheng Hua Yu granule and Cao Xian Yi Gan capsule) appear to be more effective than the other TCPMs.